The present invention provides a method of treating cancer with a combination of IL-2 and an integrin-binding-Fc fusion protein. The methods of the invention can be applied to a broad range of cancer types.

The present invention relates, in part, to agents that bind CD8 and their use as therapeutic and diagnostic agents. The present invention further relates to pharmaceutical compositions comprising the CD8 binding agents and their use in the treatment of various diseases, including, for example, cancers.

The disclosure relates to methods of diagnosis and prognosis, compositions for immunotherapies, methods of improving said compositions, and immunotherapies using the same (e.g., T cells, non-T cells, TCR-based therapies, CAR-based therapies, bispecific T-cell engagers (BiTEs), and/or immune checkpoint blockade).

The present invention is directed to novel IL-15/IL-15Rα heterodimeric Fc fusion proteins and uses thereof. The IL-15/IL-15Rα heterodimeric Fc fusion proteins can be administered to a patient to treat cancer. In some cases, the IL-15/IL-15Rα heterodimeric Fc fusion protein is administered in combination with a checkpoint blockage antibody such as a PD-1 antibody.

Disclosed herein are compositions related to conjugated polypeptides with MTA/ADO-degrading enzyme activity. The conjugated polypeptides are engineered to allow for maximal conjugation while maintaining catalytic activities. Also disclosed are nucleic acids, expression vectors, and host cells related to the conjugated polypeptides. Further disclosed are methods of using the pharmaceutical formulations comprising above to treat cancer.

Provided herein are binding polypeptides that specifically bind PD-1. More specifically, provided herein are fusion proteins, including multivalent and/or multispecific constructs and chimeric antigen receptors, that bind PD-1. Also provided are pharmaceutical compositions containing the polypeptides, nucleic acid molecules encoding the polypeptides and vectors and cells thereof, and methods of use and uses of the provided PD-1 binding polypeptides for treating diseases and conditions, such as cancer.

Immunomodulating polynucleotides are disclosed. The immunomodulating polynucleotides may contain 5-modified uridine, 5-modified cytidine, a total of from 6 to 16 nucleotides, and/or one or more abasic spacers and/or internucleoside phosphotriesters. Also disclosed are conjugates containing a targeting moiety and one or more immunomodulating polynucleotides. The immunomodulating polynucleotides and conjugates may further contain one or more auxiliary moieties. Also disclosed are compositions containing the immunomodulating polynucleotides or the conjugates containing one or more stereochemically enriched internucleoside phosphorothioates. Further disclosed are pharmaceutical compositions containing the immunomodulating polynucleotides or the conjugates and methods of their use.

Compositions comprising memory T cell Targeting Constructs comprising an anti-T cell antibody or antigen-binding portion thereof linked to a near-infrared photoactivated cytotoxin, e.g., a photoactive adduct of an infrared dye, and methods of use thereof for reducing numbers of pathogenic T cells selectively in peripheral tissues e.g., for treating inflammatory and autoimmune diseases.

Disclosed herein is a method of providing an anti-cancer immunity in a subject with a bone metastatic cancer. The method involves co-administering to the subject an effective amount of a gamma-delta T cell stimulating agent and an effective amount of a γδ CAR T cell that binds a tumor antigen, such as a prostate antigen for bone metastatic prostate cancer, or a breast cancer antigen for bone metastatic breast cancer. Also disclosed herein is a recombinant T cell that expresses a gamma-delta T cell receptor (TCR) and a chimeric antigen receptor (CAR) polypeptide.

The present invention is based on the seminal discovery that targeted immunomodulatory antibodies and fusion proteins can counter act or reverse immune tolerance of cancer cells. Cancer cells are able to escape elimination by chemotherapeutic agents or tumor-targeted antibodies via specific immunosuppressive mechanisms in the tumor microenvironment and such ability of cancer cells is recognized as immune tolerance. Such immunosuppressive mechanisms include immunosuppressive cytokines (for example, Transforming growth factor beta (TGF-β)) and regulatory T cells and/or immunosuppressive myeloid dendritic cells (DCs). By counteracting tumor-induced immune tolerance, the present invention provides effective compositions and methods for cancer treatment, optional in combination with another existing cancer treatment. The present invention provides strategies to counteract tumor-induced immune tolerance and enhance the antitumor efficacy of chemotherapy by activating and leveraging T cell-mediated adaptive antitumor immunity against resistant or disseminated cancer cells.